NAP1L2 Drives Mesenchymal Stem Cell Senescence and Suppresses Osteogenic Differentiation [ChIP-Seq]

Changes in these genes are probably a consequence of aging, and the real regulators governing BMSC senescence and osteogenesis are still unclear.In the current study, we report that nucleosome assembly-related protein NAP1L2 serves as an important regulator of both the senescence and osteogenic differentiation of BMSCs through inhibition of NF-κB signaling and recruitment of SIRT1 to deacetylate the H3K14ac level on promoters of osteogenic genes. Thus, targeting NAP1L2 using an aging antagonist such as NMN would benefit aging-related disease. Examination of histone modification in non-target control and knockdown Nap1l2 C3H10T1/2 cells

上述基因的表达改变可能是衰老的继发结果，而真正调控骨髓间充质干细胞（Bone Marrow Mesenchymal Stem Cells, BMSCs）衰老与成骨过程的核心调控因子仍未明确。本研究证实，核小体组装相关蛋白NAP1L2是调控BMSCs衰老及成骨分化的重要调控因子，其通过抑制核因子κB（Nuclear Factor-κB, NF-κB）信号通路，并招募沉默信息调节因子1（Sirtuin 1, SIRT1），以降低成骨基因启动子区域的组蛋白H3第14位赖氨酸乙酰化（H3K14ac）水平。因此，利用烟酰胺单核苷酸（Nicotinamide Mononucleotide, NMN）等衰老拮抗剂靶向调控NAP1L2，将有望为衰老相关疾病的治疗提供新策略。本研究还对非靶向对照及Nap1l2敲低的C3H10T1/2细胞进行了组蛋白修饰检测。